Neglect is the most common but least studied form of child maltreatment, with some of the most serious long- term consequences for child development. Behavioral and psychosocial interventions are frequently ineffective, possibly due to inherent biological differences in mothers who neglect their offspring. Rodent and more recent human research has demonstrated the importance of the neuropeptide, oxytocin, in facilitating social and maternal behaviors. The Principal Investigator was recently demonstrated that mothers with an insecure/dismissing pattern of adult attachment, as determined from the Adult Attachment Interview, show reduced brain reward system activation and impaired oxytocin production when engaging with their own infant. This proposal aims to determine whether intranasal oxytocin enhances maternal brain and behavioral responses to infant cues, as a possible neuropharmacological intervention for maternal neglect. One hundred and twenty first time mothers and their term infants will be enrolled to participate in a randomized, placebo- controlled crossover study of intranasal oxytocin. Functional MRI brain responses to infant face cues will be measured, as well as videotaped behavioral responses of mothers during a free-play interaction and a modified still-face procedure. Eye tracking technology will also be utilized in the scanner to determine whether oxytocin alters patterns of eye gaze when mothers view infant face images. It is hypothesized that intranasal oxytocin, compared with placebo, will result in increased activation of mesocorticolimbic dopamine reward regions in the brain, in response to own vs. unknown infant face cues. This response will also be associated with enhanced infant eye gaze in the oxytocin treatment condition. Mothers who receive intranasal oxytocin will also score higher on an overall measure of maternal sensitivity during a free play interaction (the CARE-Index), and will display more emotionally contingent responses with their infant during a modified still-face procedure. Interaction effects will be explored between treatment condition, mother's attachment classification and, in fMRI sessions, infant face affect (happy vs. sad). Finally, it is hypothesized that brain reward activation will be associated with other indirect measures of emotional neglect in mothers, including maternal sensitivity, eye gaze when viewing sad infant faces, and the contingency of maternal responses to infant cues during the modified still-face procedure. We anticipate that these results will be the basis for future randomized, controlled intervention studies of intranasal oxytocin in maternal neglect. PUBLIC HEALTH RELEVANCE: Child neglect is a significant public health issue in the United States, with serious long- term consequences for child development and behavior. This project aims to determine whether a natural hormone, oxytocin, may enhance a mother's bonding response to her baby, as measured by functional MRI and videotaped mother-infant interactions. The hope is that this may lead to a drug treatment for disorders of mother-infant attachment.